Novel application of IGF-I and IGFBP-3 generation tests in the diagnosis of growth hormone axis disturbances in children with beta-thalassaemia

OBJECTIVE Children with beta -thalassaemia major (beta -thal) frequently ha ve growth retardation in the presence of low serum IGF-I and a normal GH re sponse to pharmacological stimulation suggesting that they have GH insensit ivity (GHIS). This study was carried out to study the cause of their growth retardation. DESIGN We studied IGF-I and IGFBP-3 generation after exogenous GH administr ation for four days, in 15 prepubertal controls (C) and 41 prepubertal beta -thal patients divided into three groups according to their growth status: (Group 1) 15 with normal growth (N-thal) (Group 2) 16 with decelerated gro wth (D-thal) and (Group 3) 10 with short stature (S-thal), in order to dete rmine whether GHIS is the cause of their growth retardation. MEASUREMENTS IGF-I and IGFBP-3 were measured daily, before and for 4 days a fter daily administration of 0.1 IU/kg hGH, in 3 groups of prepubertal beta -thal patients and normal controls. RESULTS N-thal and C had similar basal serum IGF-I (142 +/- 52 and 196 +/- 56 ng/ml, respectively) and IGFBP-3 concentrations (2.07 +/- 0.49 and 2.66 +/- 0.41 mg/l, respectively) as well as a similar percent increase of IGF-I (101 +/- 23% and 104 +/- 37%, respectively) and IGFBP-3 (52 +/- 36%, and 3 8 +/- 14%, respectively) during the generation tests. S-thal and D-thal had significantly lower basal IGF-I and IGFBP-3 concentrations (85 +/- 42 and 101 +/- 36 ng/ml; and 1.60 +/- 0.49 and 1.79 +/- 0.52 mg/l, respectively) a s compared to N-thal and C (P < 0.001 and P < 0.005, respectively), and a s ignificantly higher percent increase of IGF-I and IGFBP-3 during the genera tion tests (249 +/- 43 and 161 +/- 76%; and 121 +/- 99 and 73 +/- 35%, resp ectively) as compared to N-thal and C (P < 0.0001 and P < 0.01, respectivel y). Twenty-five percent of the growth retarded patients had classic GH defi ciency (GHD) and percent increases of IGF-I and IGFBP-3 in the generation t ests (164 +/- 86% and 80 +/- 49%, respectively) which were similar to those of the remaining growth-retarded children. CONCLUSION The greater percent increases of IGF-I and IGFBP-3 in the genera tion tests of the growth retarded beta -thal patients, both with and withou t GHD, strongly suggest impaired GH secretion rather than GHIS as the cause of their growth retardation. We conclude that the IGF-I and IGFBP-3 genera tion tests are useful tools for the study not only of GHIS but also of GH s ecretory disorders in patients with beta -thal and short stature that can e asily be performed in an outpatient setting as an initial test to identify the patients that may benefit from GH therapy.